Treating mice with radioactive strontium results in local irradiation of bone marrow and bone and the destruction of cellular elements which depend upon the microenvironment of the bone marrow for differentiation. Although T and B cell immunity and other hemopoietic cell functions appear to be relatively normal in these animals, a number of host resistance phenomena are markedly altered. Many of these normal host resistance events appear to be the result of alterations in the control of immune reactions. Recent studies in our laboratory have demonstrated that suppressor T cells obtained from animals treated with 89Sr are easily activated and become immunosuppressive in times and under conditions when normal immunosuppressive activity does not occur. It is our intention to determine what mechanism of control is altered by radiation of the bone marrow microenvironment. We will determine if there is cellular involvement in this loss of control and whether there are humoral immunoregulatory factors which have become altered. If a regulatory cell is involved we will try to determine what type or types of cells they are. It will be determined whether immunosuppressive cells become activated in response to a positive stimulus or rather an escape from a normally inhibitory control. If the regulation involves only cell to cell interaction, we will determine whether any of the surface antigens, histocompatibility and others are involved in this control. Assay methods will include in vitro primary antibody response using the Mishell-Dutton assay system and adoptive transfer in inbred mice. We will also use in vitro culture systems to measure function of the suppressor cells generated in strontium treated mice.